Host resistance to cancer almost certainly involves multiple immunospecific and nonspecific mechanisms. Compelling in vitro evidence suggests an innate system of resistance involving macrophages and natural killer cells, and emerging tumors provoking immune responses. Accordingly, these experiments address a crucial issue: How do malignant cells in vivo evade destruction? The experimental approach will be to examine the significance and causation of tumor-related anti-\ inflammation. We have determined that during chemical induction of cancer with 3-methylcholanthrene, a depression in macrophage responses occurs which is positively correlated with tumor development in mice but not in rats. Large autochthonous tumors did not alter macrophage responses, although such was observed with transplanted tumors. In culture, tumors produced at least two inhibitors of inflammation, one of which is a low-molecular-weight peptide.